{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:00:39Z","timestamp":1783483239886,"version":"3.55.0"},"reference-count":38,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The prognosis of several human malignancies has dramatically improved after the introduction of tyrosine kinase inhibitors (TKIs); however, their use has been associated with a large spectrum of adverse events, including symptomatic biliary disorders. In the phase III trial of lenvatinib in radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) patients, gallbladder (GB) and biliary duct (BD) diseases and complications were reported. We evaluated symptomatic biliary disorders during treatment with lenvatinib in real-life practice to provide a more exhaustive understanding of its toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We retrospectively evaluated all consecutive patients treated with lenvatinib in our center for progressive RAI-refractory DTC, excluding those who underwent cholecystectomy before the start of therapy. We report all radiologically confirmed symptomatic GB\/BD disorders, which were subsequently treated with cholecystectomy, and we describe their management along with relevant biochemical and histological findings. All available GB\/BD imaging of patients who developed biliary toxicity during lenvatinib was reviewed by a single experienced radiologist, including computed tomography scans performed for tumor assessment at baseline and during TKI therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Five patients (14.7%) developed symptomatic radiologically confirmed biliary disease after a median time of 4.4 months of lenvatinib treatment [interquartile range 3.4\u201314.4 months] and thus underwent cholecystectomy. A scheduled surgical approach was possible only in two cases; in the remaining patients, presurgical TKI interruption was shorter than one week. After wound healing, treatment was resumed by all subjects. Three patients showed mild biochemical alterations in the two previous monthly follow-up visits. Before the start of treatment, GB\/BD abnormalities were radiologically detected only in one case.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In our cohort, an unexpectedly high proportion of RAI-refractory DTC patients treated with lenvatinib developed a symptomatic biliary disorder with the need of surgical intervention. Further studies are required to optimize the diagnosis and treatment of patients at higher risk of developing a symptomatic GB\/BD disease during assumption of lenvatinib.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2019.0355","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T05:18:25Z","timestamp":1576732705000},"page":"229-236","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Symptomatic Biliary Disorders During Lenvatinib Treatment for Thyroid Cancer: An Underestimated Problem"],"prefix":"10.1177","volume":"30","author":[{"given":"Alice","family":"Nervo","sequence":"first","affiliation":[{"name":"Oncological Endocrinology Unit, Department of Medical Sciences, Citt\u00e0 della Salute e della Scienza Hospital, University of Turin, Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Ragni","sequence":"additional","affiliation":[{"name":"Oncological Endocrinology Unit, Department of Medical Sciences, Citt\u00e0 della Salute e della Scienza Hospital, University of Turin, Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Gallo","sequence":"additional","affiliation":[{"name":"Oncological Endocrinology Unit, Department of Medical Sciences, Citt\u00e0 della Salute e della Scienza Hospital, University of Turin, Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ferraris","sequence":"additional","affiliation":[{"name":"Division of Diagnostic Imaging, Department of Surgical Sciences, Citt\u00e0 della Salute e della Scienza Hospital, University of Turin, Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Fonio","sequence":"additional","affiliation":[{"name":"Division of Diagnostic Imaging, Department of Surgical Sciences, Citt\u00e0 della Salute e della Scienza Hospital, University of Turin, Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Piovesan","sequence":"additional","affiliation":[{"name":"Oncological Endocrinology Unit, Department of Medical Sciences, Citt\u00e0 della Salute e della Scienza Hospital, University of Turin, Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Arvat","sequence":"additional","affiliation":[{"name":"Oncological Endocrinology Unit, Department of Medical Sciences, Citt\u00e0 della Salute e della Scienza Hospital, University of Turin, Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,2,14]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-18-0116"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0020"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-2838"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2017.02.009"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60421-9"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1406470"},{"key":"e_1_3_3_8_2","first-page":"1643","article-title":"Lenvatinib in advanced radioiodine-refractory thyroid cancer: a snapshot of real-life clinical practice","volume":"38","author":"Nervo A","year":"2018","unstructured":"Nervo A, , Gallo M, , Sam\u00e0 MT, , Felicetti F, , Alfano M, , Migliore E, , Marchisio F, , Berardelli R, , Arvat E, , Piovesan A. 2018. Lenvatinib in advanced radioiodine-refractory thyroid cancer: a snapshot of real-life clinical practice. Anticancer Res, 38:1643\u20131649.","journal-title":"Anticancer Res"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2017.0205"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S191499"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.05.031"},{"key":"e_1_3_3_12_2","unstructured":"U.S. Food and Drug Administration. Summary of product characteristics\u2014Lenvatinib. Available at https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/206947s007lbl.pdf (accessed May13 2019)."},{"key":"e_1_3_3_13_2","unstructured":"European Medicines Agency. Summary of product characteristics\u2014Lenvatinib. Available at https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/lenvima-epar-product-information_en.pdf (accessed May13 2019)."},{"key":"e_1_3_3_14_2","first-page":"302","article-title":"Acute acalculous cholecystitis in patients with clear cell renal cell carcinoma treated with sunitinib: report of two cases","volume":"6","author":"Furubayashi N","year":"2014","unstructured":"Furubayashi N, , Negishi T, , Hirata Y, , Taguchi K, , Nakamura M. 2014. Acute acalculous cholecystitis in patients with clear cell renal cell carcinoma treated with sunitinib: report of two cases. J Clin Med Res, 6:302\u2013304.","journal-title":"J Clin Med Res"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-13-242"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(13)70215-8"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_3_3_18_2","unstructured":"National Cancer Institute. 2010. Common terminology criteria for adverse events (CTCAE) version 4.03. Available at https:\/\/evs.nci.nih.gov\/ftp1\/CTCAE\/CTCAE_4.03\/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf (accessed May13 2019)."},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2018.06.019"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2018.11.004"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.27.5.775"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.4081\/cp.2014.635"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.3816\/CGC.2009.n.011"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/1752-1947-6-69"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.07.8170"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa075853"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.18.7815"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdq731"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-11-313"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.72.7297"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00423-006-0103-z"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2005.00476.x"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-012-1839-5"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2016.12.035"},{"key":"e_1_3_3_35_2","doi-asserted-by":"crossref","first-page":"201529","DOI":"10.5402\/2011\/201529","article-title":"Acalculous cholecystitis in a patient with hepatocellular carcinoma on sorafenib","volume":"2011","author":"Sanda M","year":"2011","unstructured":"Sanda M, , Tamai H, , Deguchi H, , Mori Y, , Moribata K, , Shingaki N, , Ueda K, , Inoue I, , Maekita T, , Iguchi M, , Yanaoka K, , Oka M, , Ichinose M. 2011. Acalculous cholecystitis in a patient with hepatocellular carcinoma on sorafenib. ISRN Gastroenterol, 2011:201529.","journal-title":"ISRN Gastroenterol"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.11.7432"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinimag.2013.08.012"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00261-017-1050-6"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.03.005"}],"container-title":["Thyroid\u00ae"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/thy.2019.0355","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2019.0355","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2019.0355","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:06:17Z","timestamp":1777586777000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/thy.2019.0355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["10.1089\/thy.2019.0355"],"URL":"https:\/\/doi.org\/10.1089\/thy.2019.0355","relation":{},"ISSN":["1050-7256","1557-9077"],"issn-type":[{"value":"1050-7256","type":"print"},{"value":"1557-9077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2]]}}}